Several publications describe conversions of cocaine to anhydroecgonine where the conversion is effected by heating cocaine in aqueous acid (hydrochloric or sulphuric acid) or with benzoic acid for several hours (de Jong, Recl. Trav. Chim. Pays-Bas, 56 (1937), pages 187-201 and Chem. Ber., 21 (1888), pages 3029-3045). At the time of the references cited above, the analytical methods available for the qualitative and quantitative determination of chemical compounds were limited, which makes the results obtained highly uncertain. Furthermore there is a lack of precise descriptions of how the reactions were carried out.
Several attempts to convert ecgonine or cocaine to anhydroecgonine in alkaline solutions or by heating in water, giving poor results, have also been described. In fact it seems that alkaline solutions favour isomerisation (de Jong, Recl. Trav. Chim. Pays-Bas, 56 (1937), pages 192-194.
In later references Anhydroecgonine and esters thereof have been prepared by hydrolysis of cocaine in aqueous hydrochloric acid followed by dehydration with phosphorus oxychloride (J. Amer. Chem. Soc., 82 (1960), page 4643 and EP-A1-604 355 ). Although both the hydrolysis of cocaine and the dehydration of ecgonine produces high yields, it is a serious drawback to this method that the reaction mixture becomes syrupy during the dehydration step which makes stirring almost impossible. Using SOCl.sub.2 as dehydrating agent causes similar problems.
Neither of these methods are thus suitable for large-scale production.
It has now surprisingly been found that esters of anhydroecgonine can be prepared in large-scale from cocaine or derivatives thereof using a convenient, high-yielding, one-pot synthesis.
The esters prepared according to the invention are useful intermediates in the preparation of pharmaceutically active tropane derivatives, see EP-A1-604 355).